Pitolisant reduces cataplexy in narcolepsy patients
medwireNews: Pitolisant, a histamine H3 receptor inverse agonist, has shown promise for the treatment of cataplexy in patients with narcolepsy, investigators report.
Seven weeks of treatment with the drug was associated with a 75% reduction in the frequency of weekly cataplexy episodes compared with baseline and about a 50% reduction compared with placebo.
This finding adds to previous reports of improvement in excessive daytime sleepiness with the drug, notes the team.
“In narcolepsy, pitolisant appears to be active against not only excessive daytime sleepiness but also cataplexy, the two major manifestations of the disease,” say Jean-Charles Schwartz (Bioprojet Pharma, Paris, France) and fellow members of the HARMONY-CTP study group.
“If these data are confirmed in long-term studies, pitolisant might constitute a useful first-line therapy for narcoleptic patients with cataplexy (type 1 narcolepsy), for whom there are currently few therapeutic options.”
Among the 106 study patients, 54 were randomly assigned to daily pitolisant and completed 3 weeks of flexible dosing at 5, 10, or 20 mg, according to efficacy and tolerability, followed by 4 weeks of stable dosing. The remaining 51 patients received placebo.
The weekly rate of cataplexies fell from seven to nine per week at baseline to two per week among patients taking pitolisant and five per week among those taking placebo, reflecting a significant treatment effect.
The researchers note in The Lancet Neurology that the weekly cataplexy rate progressively decreased from baseline with maximum benefit reached at 5 weeks. Significant benefit was seen for each of the dosing groups, which they say “underscores the potential advantage of the flexible dosing scheme and reduces unnecessary drug exposure,” and irrespective of whether or not patients used anticataplectic treatment prior to the trial or resumed taking it concomitantly during the trial.
Pitolisant was also superior to placebo for most of the secondary endpoints. For example, Epworth Sleepiness Scale (ESS) scores fell by a significant 5.4 points with pitolisant treatment versus 1.9 points with placebo, from a baseline of 17 points. And a significantly greater proportion of patients taking pitolisant had fewer than 15 cataplexies per week and an ESS score of 10 or below, at a respective 7% and 39% versus 24% and 18% with placebo.
Improvements on the Maintenance of Wakefulness Test, clinical and patient global impression of change, and the frequency of hallucinations were all significantly greater with pitolisant than placebo.
Pitolisant treatment was generally well tolerated, with a similar number of patients in both groups reporting adverse events. The researchers report that twice as many treatment-related adverse events were reported by patients taking pitolisant than those taking placebo, but they note that all events were mild to moderate in intensity; the only exception being one case of severe nausea that resolved after the drug was stopped. The most frequent event was headache, followed by irritability and anxiety.
In a related comment, Christian Baumann (University of Zurich, Switzerland) points out one important limitation, highlighting that the criteria used to diagnose narcolepsy were nonspecific – subjective sleepiness and experience of cataplexy. While the diagnosis was corroborated with multiple sleep latency tests, he says that the standard of these is suboptimal.
Despite this, however, he believes that “this study is important and deserves the attention of clinicians, scientists, and policymakers,” adding that approval of the compound would be “good news for clinicians, since we need more treatment options to better tailor individualised therapy for patients with narcolepsy.”
By Lucy Piper
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